The investigation on possible genetic predisposing factor(s) for susceptibility to ethanol toxicity is being continued. We have studied a total of five patients with the diagnosis of Fetal Alcohol Syndrome (FAS) under the clinical protocols. Skin fibroblasts from these patients are now being studied for possible biochemical abnormalities in the transketolase enzyme and survival of these cells in thiamine deficient medium in vitro. In a related study in animals we have recently discovered that thiamine deficiency during intra uterine development of the fetus in rats alters the response to ethanol in adulthood. Dr. Peter Martin's laboratory at Vanderbilt University has cloned a human transketolase cDNA by antibody screening of a lambda gt 11 human liver library from Clontech. This cDNA will be available for us to probe the Wernicke-Korsakoff fibroblasts which we have established in our laboratory to determine the specific genetic abnormality in transketolase enzyme with high Km for thiamine pyrophosphate which we have reported for this syndrome.